Scientists have created a molecular atlas of exercises

To understand what a healthy norm looks like and how the body adapts to exercise, scientists compared young male and female mice that voluntarily ran on a wheel for eight weeks with those that led a sedentary lifestyle. Samples of 22 different tissues were taken from the animals, and this was done at different phases of the day to take into account the influence of circadian rhythms. To obtain the most complete picture, the researchers used several methods at once. Mass RNA sequencing made it possible to see which genes are active in each tissue. Metabolomics captured small molecules involved in metabolism. Proteomics measured protein levels, particularly in four leg muscles. Special attention was paid to single‑cell sequencing — this approach provides a detailed picture, distinguishing neighboring cells by their exact identity and activity.

In addition, the scientists conducted an analysis of DNA methylation, which reveals epigenetic changes: such marks can regulate gene activity and often persist for a long time. It is important that this is the first study in which methylation analysis at the level of individual cells was applied to muscles after exercise.

The atlas showed that the body’s reorganization under the influence of exercise occurs throughout the body, but in each tissue in its own way. The changes were most pronounced in skeletal muscles, but the effect of exercise affected almost half of the genes in at least one of the 22 tissues studied. At the same time, no gene was found that changed in all tissues simultaneously, which underscores the strictly tissue‑specific nature of the body’s response. The level of detail at the level of individual cells turned out to be particularly valuable: if you assess changes on average across the entire tissue, many important shifts are simply lost. For example, in muscles, exercises changed methylation in some types of cells while leaving others virtually unchanged.

Circadian rhythms also turned out to be a significant factor. In most tissues, the most noticeable changes occurred during the active phase of the day, whereas the hypothalamus, kidneys, and lungs behaved differently. Significant differences were also identified between the sexes: In females, the transcriptional responses were broader, and the patterns of gene expression and epigenetic responses differed from those observed in males.

Another important result was a signature consisting of 51 genes — a set that makes it possible to distinguish trained muscle from untrained muscle not only in mice but also in humans. In the future, such a signature may help in the search for biomarkers, as well as in the study of atrophy and muscle dysfunction.

The created atlas is a general scientific foundation that other researchers can rely on. With its help, it is possible to purposefully study individual genes or metabolic pathways in order to thoroughly examine the mechanisms behind the effects of exercise. The atlas also paves the way for more personalized approaches to training, taking into account gender and time of day, since the body’s response to physical activity varies from person to person. In addition, it provides material for identifying new targets that can improve recovery, performance, and muscle health.

The authors say that the key to understanding the benefits of exercise is to view the body as a whole: not to limit oneself to just muscles, but to also look at other organs; not to be satisfied with average indicators, but to take into account the differences between cell types. At the same time, many questions remain: how enduring are the changes resulting from training, how long does it take for them to become established, and do cells retain a memory of the loads after months or even years? The molecular atlas serves as a starting point for decades of new research that will gradually reveal exactly how movement protects health and prolongs active life.